crossing96/oncoscreening huggingface dataset:
Inhibition of urinary bladder cancer cell proliferation by silibinin.	Silibinin, a natural compound extracted from milk thistle, has demonstrated antitumor properties in urinary bladder cancer cells; however, the role of TP53 gene in these effects is unclear. In order to better understand the molecular and antiproliferative mechanisms of this compound, urinary bladder cancer cells with different TP53 gene status, RT4 (low-grade tumor, wild TP53 gene), 5637 (high-grade tumor, Grade 2, mutated TP53 gene), and T24 (high-grade tumor, Grade 3, mutated TP53 gene) were treated with several concentrations of silibinin (1, 5, 10, 50, 100, and 150 μM). Cytotoxicity, prooxidant effect, morphological changes, cell migration, cell cycle progression, global methylation profile, and relative expression of HOXB3, c-MYC, PLK1, SMAD4, SRC, HAT, HDAC, and RASSF1A genes were evaluated. The silibinin presented cytotoxic and prooxidant effects in the three cell lines. In mutated TP53 cells, significant interference in cell migration and cell cycle arrest at the G2/M phase was observed. Additionally, silibinin induced global DNA hypomethylation in the highest grade tumor cells. For wild-type TP53 cells, a sub-G1 apoptotic population was present. Furthermore, there was modulation of gene expression responsible for cell growth (SMAD and c-MYC), migration (SRC), cell cycle kinetics (PLK1), angiogenesis (HOXB3), and of genes associated with epigenetic events such as DNA acetylation (HAT) and deacetylation (HDAC). In conclusion, the silibinin inhibited the urinary bladder tumor cell proliferation independently of TP53 status; however, cell cycle effects, gene expression changes, and alteration of cell migration are dependent on TP53 status. © 2020 Wiley Periodicals, Inc.	bladder
MMR deficiency in urothelial carcinoma of the bladder presents with temporal and spatial homogeneity throughout the tumor mass.	"BACKGROUND: Microsatellite instability (MSI), a hypermutator phenotype described in many cancers, has emerged as a predictive biomarker for immune checkpoint inhibitor therapy. Cancer heterogeneity represents a potential obstacle for the analysis of predicitive biomarkers. MSI has been reported in bladder cancer, but data on the possible extent of intratumoral heterogeneity are lacking. METHODS: To study MSI heterogeneity in bladder cancer, a tissue microarray (TMA) comprising 598 muscle-invasive urothelial carcinomas of the bladder was utilized to screen for MSI by immunhistochemistry with antibodies for MLH1, PMS2, MSH2, and MSH6. RESULTS: In 9 cases suspicious for MSI, MMR status was further evaluated by large section examination and polymerase chain reaction (PCR)-based analysis of microsatellites (""Bethesda panel"") resulting in the identification of 5 validated MSI cases from 448 interpretable cancers (prevalence 1.1%). MMR deficiency always involved PMS2 loss, in 3 cases with additional loss or reduction of MLH1 expression. Four cancers were MSI-high and 1 was MSI-low in the PCR analysis. Parallel sequencing revealed an inactivating MLH1 mutation in 1 tumor but no further known pathogenic MMR gene mutations were found. Immunostaining of all available 72 cancer-containing tissue blocks of the 5 confirmed bladder cancer with MSI including prior and subsequent biopsies showed complete homogeneity of the MMR protein defects and the status of the 4 MMR proteins did not markedly change in sequential resections. In all 4 cases with noninvasive precursor lesions, MSI was also detectable. CONCLUSION: These data suggest that MSI occurs early in invasive bladder cancer and immunohistochemical MMR analysis on limited biopsy material is sufficient to estimate MMR status of the entire cancer mass."	bladder
The Effect of Surgical Experience on Perioperative and Oncological Outcomes After Robot-assisted Radical Cystectomy with Intracorporeal Urinary Diversion: Evidence from a Referral Centre with Extensive Experience in Robotic Surgery.	BACKGROUND: Evidence on the learning curve for robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is limited. OBJECTIVE: To assess the effect of surgical experience (SE) on perioperative and intermediate-term oncological outcomes in a large contemporary cohort of RARC patients after accounting for the impact of intersurgeon variability. DESIGN, SETTING, AND PARTICIPANTS: The study cohort included 164 patients treated with RARC and ICUD by two surgeons between 2004 and 2017 at a single European referral centre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: For each patient, SE was defined as the total number of RARCs performed by each surgeon before the patient's operation. The relationship between SE and operative time (OT), lymph node yield (LNY), positive surgical margins (PSMs), Clavien-Dindo grade ≥2 30-d postoperative complication (CD≥2), and oncological outcomes (18-mo recurrence rate) was evaluated in multivariable linear and logistic regression models, clustering at a single-surgeon level. RESULTS AND LIMITATIONS: After adjusting for case mix, SE was associated with shorter OT (p= 0.003), lower probability of postoperative CD≥2 rates (p= 0.01), and lower 18-mo recurrence rates (p= 0.002). Conversely, SE did not predict lower PSM rates (p= 0.3) and higher LNY (p= 0.4). The relationship between SE and OT was nonlinear, with a plateau observed after 50 cases. Conversely, the relationship between SE and CD≥2 and 18-mo recurrence was linear without reaching a plateau after 88 procedures. CONCLUSIONS: SE affects perioperative and oncological outcomes after RARC with ICUD in a linear fashion, and its beneficial effect does not reach a plateau. Conversely, after 50 cases, no further improvement was observed for OT. PATIENT SUMMARY: Robot-assisted radical cystectomy with intracorporeal urinary diversion is a complex surgical procedure with a relatively long learning curve.	bladder
Gastric and duodenal ulcers, periodontal disease, and risk of bladder cancer in the Health Professionals Follow-up Study.	PURPOSE: Studies suggest that peptic ulcer and periodontal disease are positively associated with bladder cancer risk. These two factors are likely to share common biologic mechanisms such as inflammation and dysbiosis. We examined the joint association of peptic ulcer (gastric/duodenal) and periodontal disease on bladder cancer risk. METHODS: We conducted a prospective analysis among 45,185 men (563 invasive bladder cancer cases) in the Health Professionals Follow-Up Study (follow-up 1986-2016). History of ulcer and periodontal disease was self-reported at baseline and updated during the follow-up. Cox proportional hazards models estimated hazard ratio (HR) and 95% confidence interval (CI) for the joint associations of ulcers (gastric, duodenal) and periodontal disease, adjusting for age and other potential confounders. We tested for interaction using the Wald test for product terms. RESULTS: Compared with men having no history of ulcer and periodontal disease, men with a history of peptic ulcer only (HR 1.22, 95% CI 0.90-1.66) and men with a history of periodontal disease only (HR 1.19, 95% CI 0.98-1.46) were associated with higher risk of invasive bladder cancer. The highest bladder cancer risk was observed in men with a history of both peptic ulcer and periodontal disease (HR 1.52, 95% CI 1.05-2.20). Similar results were found when we stratified by ulcer types. The interactions between ulcer and periodontal disease were not statistically significant for all ulcer types (p-interaction ≥ 0.59). CONCLUSION: We did not find sufficient evidence for interaction between gastric/duodenal ulcers and periodontal disease on bladder cancer risk.	bladder
LncRNA MST1P2/miR-133b axis affects the chemoresistance of bladder cancer to cisplatin-based therapy via Sirt1/p53 signaling.	Although bladder cancer is commonly chemosensitive to standard first-line therapy, the acquisition of the resistance to cisplatin (DDP)-based therapeutic regimens remains a huge challenge. Noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs) and microRNAs, have been reported to play a critical role in cancer resistance to DDP. Here, we attempted to provide a novel mechanism by which the resistance of bladder cancer to DDP treatment could be modulated from the perspective of ncRNA regulation. We demonstrated that lncRNA MST1P2 (lnc-MST1P2) expression was dramatically upregulated, whereas miR-133b expression was downregulated in DDP-resistant bladder cancer cell lines, SW 780/DDP and RT4/DDP. Lnc-MST1P2 and miR-133b negatively regulated each other via targeting miR-133b. Both lnc-MST1P2 silence and miR-133b overexpression could resensitize DDP-resistant bladder cancer cells to DDP treatment. More important, miR-133b could directly target the Sirt1 3'-untranslated region to inhibit its expression. Inc-MST1P2/miR-133b axis affected the resistance of bladder cancer cells to DDP via Sirt1/p53 signaling. In conclusion, MST1P2 serves as a competing endogenous RNA for miR-133b to counteract miR-133b-induced suppression on Sirt1, therefore enhancing the resistance of bladder cancer cells to DDP. MST1P2/miR-133b axis affects the resistance of bladder cancer cells to DDP via downstream Sirt1/p53 signaling.	bladder
ITIH5 and ECRG4 DNA Methylation Biomarker Test (EI-BLA) for Urine-Based Non-Invasive Detection of Bladder Cancer.	Bladder cancer is one of the more common malignancies in humans and the most expensive tumor for treating in the Unites States (US) and Europe due to the need for lifelong surveillance. Non-invasive tests approved by the FDA have not been widely adopted in routine diagnosis so far. Therefore, we aimed to characterize the two putative tumor suppressor genes ECRG4 and ITIH5 as novel urinary DNA methylation biomarkers that are suitable for non-invasive detection of bladder cancer. While assessing the analytical performance, a spiking experiment was performed by determining the limit of RT112 tumor cell detection (range: 100-10,000 cells) in the urine of healthy donors in dependency of the processing protocols of the RWTH cBMB. Clinically, urine sediments of 474 patients were analyzed by using quantitative methylation-specific PCR (qMSP) and Methylation Sensitive Restriction Enzyme (MSRE) qPCR techniques. Overall, ECRG4-ITIH5 showed a sensitivity of 64% to 70% with a specificity ranging between 80% and 92%, i.e., discriminating healthy, benign lesions, and/or inflammatory diseases from bladder tumors. When comparing single biomarkers, ECRG4 achieved a sensitivity of 73%, which was increased by combination with the known biomarker candidate NID2 up to 76% at a specificity of 97%. Hence, ITIH5 and, in particular, ECRG4 might be promising candidates for further optimizing current bladder cancer biomarker panels and platforms.	bladder
Retrograde en bloc resection for non-muscle invasive bladder tumor can reduce the risk of seeding cancer cells into the peripheral circulation.	OBJECTIVE: To ascertain whether en bloc resection could reduce the risk of seeding cancer cells into the circulation during the resection of non-muscle invasive bladder cancer (NMIBC). METHODS: Patients with primary NMIBC were enrolled in this prospective study from October 2017 to May 2018. Patients were allocated to receive conventional transurethral resection of the bladder (TURB) or retrograde en bloc resection technique of the bladder tumor (RERBT). Blood samples (1 ml) for circulating tumor cell (CTC) enumeration were drawn from the peripheral vein prior to resection (PV1), immediately after resection of the tumor base (PV2), and at 12 h after resection (PV3). Intra-group comparisons of the changes in the number of CTCs identified among the PV1, PV2, and PV3 blood samples were performed in each group. RESULTS: A total of 21 patients (12 in the RERBT group and 9 in the TURB group) were recruited. For patients receiving TURB, the level of CTCs identified in PV3 was significantly higher than that in PV1 (p = 0.047). However, there was no significant difference in CTC counts before and after resection in the RERBT group. CONCLUSION: RERBT did not increase the number of tumor cells in the bloodstream.	bladder
Risk stratification metrics for bladder cancer: Comprehensive Geriatric Assessments.	Despite advances in surgical technique and perioperative care pathways, complication rates following radical cystectomy for bladder cancer remain high and perioperative outcomes for elderly patients are suboptimal. Furthermore, subjective risk assessments of patients with bladder cancer, with a high prevalence of complex comorbidity burden and risk of frailty, may result in undertreatment of patients assumed to be poor operative candidates. A critical component of preoperative patient counseling and treatment selection is accurate and objective preoperative risk appraisal. Comprehensive Geriatric Assessments are multi-domain evaluations of the medical, functional, and psychosocial aspects of health designed specifically for use in elderly patients with the objective of identifying vulnerabilities that may be targeted with interventions for improvement. While currently recommended by multiple guideline bodies for use in the preoperative evaluation of elderly patients with bladder cancer there is a paucity of data describing their use in contemporary clinical practice. Herein, then, we will describe the components of a Comprehensive Geriatric Assessments and propose strategies for their integration into the preoperative surgical workflow.	bladder
Tumour functional imaging by PET.	Carcinogenesis is a complex multistep process, characterized by changes at different levels, both genetic and epigenetic, which alter cell metabolism. Positron emission tomography (PET) is a very sensitive image modality that allows to evaluate oncometabolism. PET functionalities are immense, since by labelling a molecule that specifically intervenes in a biochemical regulatory pathway of interest with a positron-emitting radionuclide, we can easily image that pathway. Thus, PET makes possible imaging several metabolic processes and assessing risk prediction, screening, diagnosis, response to therapy, metastization and recurrence. In this paper, we provide an overview of different radiopharmaceuticals developed for PET use in oncology, with a focus on brain tumours, breast cancer, hepatocellular carcinoma, neuroendocrine tumours, bladder cancer and prostate cancer because for these cancer types PET has been shown to be valuable. Most of the described tracers are just used in the research environment, with the aim to assess if these tracers could be able to offer an improvement concerning staging/restaging, characterization and stratification of different types of cancer, as well as therapeutic response assessment. In pursuit of personalized therapy, we briefly discuss the more established metabolic tracers and describe recent work on the development of new radiopharmaceuticals, aware that there will continue to exist diagnostic challenges to face modern cancer medicine.	bladder
PD-L1 expression in bladder primary in situ urothelial carcinoma: evaluation in BCG-unresponsive patients and BCG responders.	Carcinoma in situ (CIS) is believed to be a precursor of muscle-invasive carcinomas that may arise from these flat high-grade, superficial urothelial lesions. CIS accounts for approximately 10% of all bladder tumors. Therapeutic options for urothelial CIS are limited, and in order to inhibit disease progression and recurrence, current guidelines recommend transurethral resection (TURBT) followed by intravesical administration of Bacillus of Calmette-Guerin (BCG). Approximately 30-40% of patients fail the BCG therapy with recurrence and progression of disease. In the present study, we examined the expression of PD-L1 both in neoplastic epithelial cells and in stromal inflammatory cells in patients with diagnosis of CIS primary responders and not responders to BCG therapy, in order to verify if the PD-L1 expression could identify patients resistant to BCG treatment. Moreover, we analyzed on the same cases the immunoreactivities of anti-PD-L1 MoAbs such as SP263, C23, and SP142. Our results have showed that PD-L1 expression in tumor cells and in immune cell compartment is higher in BCG-unresponsive group than in BCG responders, but only the PD-L1 22C3 expression in tumor cells seems to be associated with recurrence of disease (p = 0.035; OR 0.1204; CI 95% from 0.0147 to 1.023). Hence, our data suggest that the PD-L1 22C3 expression could help to identify CIS that fail the BCG therapy, supporting the hypothesis that enhanced levels of intratumoral PD-L1 22C3 expressed by the tumor cells may explain the failure of BCG immunotherapy.	bladder
Increasing use of positron emission tomography among medicare beneficiaries undergoing radical cystectomy.	OBJECTIVE: To examine factors associated with PET scan use in the pre-operative evaluation of patients diagnosed with bladder cancer. METHODS: Using SEER-Medicare data, we identified bladder cancer patients who underwent radical cystectomy from 2006 to 2011 (n = 4,138). The primary outcome was PET scan use within 6 months before surgery. To examine predictors of PET scan use, we fit a mixed logit model with health service area as a random effect to account for patients nested within health service areas. We also calculated the adjusted probability of use over time and examined variation among the highest volume surgeons. RESULTS: Among the 4,138 patients, 406 (10%) received a pre-operative PET scan. The adjusted probability of a patient undergoing a PET scan increased from 0.04 in 2004 to 0.10 in 2011 (p < .001). Among the 78 highest volume surgeons, there was significant variation in PET scan use (p < .001). Patients with non-urothelial histology, measurement of alkaline phosphatase levels, and receipt of neoadjuvant chemotherapy were more likely to receive PET scan (all p < .05). CONCLUSION: Use of PET prior to radical cystectomy doubled over a 5-year period, suggesting its increased use in patients with muscle-invasive bladder cancer, particularly those with high-risk disease. Whether its use is warranted and improves patient outcomes is not clear and requires further studies.	bladder
Plasminogen activator inhibitor-2 (PAI-2) overexpression supports bladder cancer development in PAI-1 knockout mice in N-butyl-N- (4-hydroxybutyl)-nitrosamine- induced bladder cancer mouse model.	BACKGROUND: Accumulating evidence suggests that plasminogen activator inhibitor-1 (PAI-1) plays an important role in bladder tumorigenesis by regulating cell cycle. However, it remains unclear whether and how inhibition of PAI-1 suppresses bladder tumorigenesis. METHODS: To elucidate the therapeutic effect of PAI-1 inhibition, we tested its tumorigenicity in PAI-1 knockout (KO) mice exposed to a known bladder carcinogen. RESULTS: PAI-1 deficiency did not inhibit carcinogen-induced bladder cancer in mice although carcinogen-exposed wild type mice significantly increased PAI-1 levels in bladder tissue, plasma and urine. We found that PAI-1 KO mice exposed to carcinogen tended to upregulate protein C inhibitor (PAI-3), urokinase-type plasminogen activator (uPA) and tissue-type PA (tPA), and significantly increased PAI-2, suggesting a potential compensatory function of these molecules when PAI-1 is abrogated. Subsequent studies employing gene expression microarray using mouse bladder tissues followed by post hoc bioinformatics analysis and validation experiments by qPCR and IHC demonstrated that SERPING1 is further downregulated in PAI-1 KO mice exposed to BBN, suggesting that SERPING1 as a potential missing factor that regulate PAI-2 overexpression (compensation pathway). CONCLUSIONS: These results indicate that serpin compensation pathway, specifically PAI-2 overexpression in this model, supports bladder cancer development when oncoprotein PAI-1 is deleted. Further investigations into PAI-1 are necessary in order to identify true potential targets for bladder cancer therapy.	bladder
Oxidant-antioxidant levels in patients with bladder tumours.	PURPOSE: We have aimed to determine whether oxidants-antioxidants play a role in the etiopathogenesis of bladder tumour by measuring their levels in the serums of patients with bladder tumour. MATERIAL METHOD: Thirty patients with bladder tumour with superficial bladder tumour and 27 normal healthy volunteers were included in the study. Four cc of venous blood was taken from these patients and volunteers in the control group and centrifuged at 5000 rpm for 10 minutes and divided into serum and plasma. The activities of xanthine oxidase, glutathione reductase, glutathione-s transferase, reduced glutathione and superoxide dismutase enzymes in serum were then measured spectrophotometrically. FINDINGS: Antioxidant parameters (glutathione-s-transferase, reduced glutathione, superoxide dismutase and glutathione reductase) in the serum of patients with bladder tumours were found statistically significantly lower than control group (p < .05). On the other hand, xanthine oxidase which is an oxidant indicator, was found significantly higher in patients with bladder cancer than control group (p < .05). CONCLUSION: Oxidative stress is effective in the etiopathogenesis of bladder tumour. We, therefore, believe that antioxidants are protective against bladder tumours and will be effective in the treatment of bladder tumours.	bladder
[Urinary bladder cancer as a late sequela of spinal cord injury : Decision-making aids for assessment of this causal association].	BACKGROUND: There is to date no convincing literature that has assessed the association between traumatic spinal cord injury (SCI) and the later development of urinary bladder cancer. The aim of this work is to present medical experts as well as the national accident insurance and the social courts decision-making aids based on the latest medical scientific knowledge, for assessment of this causal association. MATERIALS AND METHODS: A study conducted between April 1998 and March 2017 in the BG Trauma Hospital Hamburg forms the basis for the decision-making aids. Urinary bladder cancer was diagnosed in 32 out of 6432 treated outpatient and inpatient SCI patients. Furthermore, relevant published literature was taken into consideration for the decision-making aids. RESULTS: It was found that urinary bladder cancer in SCI patients occurs at a considerably younger age as compared to the general population, more frequently shows muscle invasive carcinoma with a higher grade at first diagnosis and a higher proportion of the more aggressive squamous cell carcinoma than that of the general population. Correspondingly, the survival time is extremely unfavorable. For medical experts a matrix was compiled where the various influencing factors, either for or against the recognition of an association between SCI and urinary bladder cancer, were weighted according to their relevance. CONCLUSION: The results showed that urinary bladder cancer in SCI patients differs considerably from that of able-bodied patients. These differences drastically shorten the survival time. A study on patients with spina bifida, i.e., a congenital spinal cord disorder, corroborates these observations. They indicate histopathological differences that have so far been intangible.	bladder